Colorectal cancer causes a subacute form of chronic inflammatory demyelinating polyneuropathy in both mouse and non-human primate models, according to a study published in Nature Communications. Researchers observed that tumor-bearing mice developed peripheral neuropathy linked to subtle locomotor deficits without showing overt hypersensitivity.
In the rodent models, the research revealed widespread alterations in pro-inflammatory cytokines and lipid metabolites within peripheral nerves. Scientists linked macrophage accumulation, myelin decompaction, and ryanodine receptor oxidation to dysfunctional calcium homeostasis and reduced spike amplitude in sensory neurons.
Primate Findings
The research team identified parallel pathological features in rhesus macaques diagnosed with colorectal cancer. In the non-human primates, alterations in plasma inflammatory mediators and lipid metabolites were associated with neuropathy and macrophage accumulation in peripheral nerves. These cross-species results indicate that tumor-induced inflammatory neuropathy represents an under-reported risk factor for colorectal cancer survivors.
Colorectal cancer survivors face an elevated risk of neurological complications, particularly peripheral neuropathy and chronic pain. Although pre-existing neuropathy was previously recognized as a risk factor for chronic pain, tumor-induced neuropathy had not been firmly established in pre-clinical models before this study.
Research Team and Funding
Investigators at The University of Texas MD Anderson Cancer Center led the project in collaboration with researchers from Columbia University College of Physicians and Surgeons and the Michale E. Keeling Center for Comparative Medicine and Research. The author team included Caitlyn M. Gaffney, Angela M. Casaril, Yanyan Jiang, Nathan T. Fiore, Jialu Liu, Karen M. Valadez, Elizabeth A. Kolb, Fisher R. Cherry, Iqbal Mahmud, Bo Wei, Philip L. Lorenzi, Lei Shi, Theresa A. Guise, Kenneth Dunner Jr., Steven R. Reiken, Carolyn L. Hodo, Peter M. Grace, Rajasekaran Mahalingam, and Andrew J. Shepherd. Technical assistance was provided by Francisco Rámirez Nangucé Sr.
Funding sources included Department of Defense PRCRP award HT9425-25-1-0632, the MD Anderson Cancer Neuroscience Program, and a Rita Allen Foundation Award in Pain to Shepherd. Guise received support as a CPRIT Scholar under Established Investigator Award RR190108. The Small Animal Imaging, Histopathology, Metabolomics, and High-Resolution Electron Microscopy Facilities at MD Anderson received support under NIH and NCI award P30CA016672. The manuscript was received on July 25, 2024, accepted on August 4, 2026, and officially published on August 12, 2026.
